tbuckley/cabot-search huggingface dataset:
Identifying trends for high symptom burden across the care continuum in adolescents and young adults (AYA) with hematologic malignancies.
Authors: Sarah Elizabeth Monick, Collin Hanson, Amy Yuan Wang, Sang Mee Lee, Karen Sarah Hoehn, Fay J. Hlubocky, Wendy Stock, Adam Duvall, Jennifer Lynn McNeer, Tara O. Henderson, Christopher Daugherty
Journal: Journal of Clinical Oncology (2022)

10019 Background: Cancer in adolescence and young adulthood is a non-normative life event associated with profound long-term physical and psychosocial consequences. Prior studies specifically demonstrate AYA patients with hematologic malignancies experience high symptom burden with poor quality of life. Here, we describe trends and factors associated with high symptom burden in patients treated at a multi-disciplinary AYA leukemia clinic at an academic medical center. Methods: The Edmonton Symptom Assessment Scale [ESAS] (measuring physical symptoms) and Brief Symptom Inventory-18 [BSI-18] (measuring psychological distress) were administered at baseline, 3 months, and 6 months from initial survey. Baseline demographic and treatment characteristics were collected. All patients had leukemia or lymphoma, were on treatment or in survivorship, and had access to a palliative care provider who was integrated into the clinic. Data was analyzed using Wilcox ranked sum test and linear mixed-effects model testing. Results: Of the 31 patients (median age 29 years, range 18-43) who completed surveys, 25 (80%) completed surveys at 6 months; 48% were female, 58% were white, 16% lived alone, 28% were single, 37% had children, 54% completed college, and 35% had an annual household income ≥ $75,000. Phases of care included 52% on intensive frontline/salvage treatment, 19% in maintenance (i.e. lower intensity) therapy, 16% as recent stem cell transplant (SCT) recipients (&lt; 1 year since date of transplant), and 13% in survivorship. Overall, ESAS scores among patients were similar regardless of care phases; however, patients on frontline/salvage therapy reported higher fatigue than those in maintenance (p = 0.01). Moderate-severe symptoms (defined as ESAS &gt; 3), including tiredness, anxiety, poor appetite, and poor feeling of well-being, were reported regardless of phase of care. At 6 months, there was no significant change in BSI-18 scores compared to baseline, while tiredness (p = 0.02), depression (p = 0.01), and constipation (p = 0.02) improved; no ESAS scores worsened. Age ≥ 30 was associated with worsening anxiety (p = 0.01) at 6 months vs baseline, while no statistically significant differences in ESAS scores were observed among race, education, relationship status, presence of children, living arrangement, or income. Conclusions: AYA patients with hematologic malignancies experience high symptom burden independent of demographic characteristics or phase of care. These findings highlight the need for standard symptom screening at each visit and the importance of incorporating supportive care throughout the continuum.
RONC-13. Change in hippocampus volume as a function of radiation dose: Results from a prospective trial with standardized imaging and morphometric evaluation
Authors: Matthew Hall, Yazmin Odia, Katherine Von Werne, Toba Niazi, Ossama Maher, Ziad Khatib, Alexander Mohler, Rupesh Kotecha, Noah Kalman, Martin Tom, Kevin Abrams, Reshma Naidoo, Michael Chuong, Andrew Wroe, Alonso Gutierrez, Minesh Mehta
Journal: Neuro-Oncology (2022)

Abstract PURPOSE/OBJECTIVES: MRIs were prospectively collected at baseline and during follow-up in pediatric and young adult brain tumor patients (Age&amp;lt;35) to measure volumetric changes in multiple brain substructures with neurocognitive, laboratory, and quality-of-life assessments. In this planned interim analysis, we model early outcomes for change in hippocampal volume at 6 and 12 months following radiotherapy. MATERIALS/METHODS: As of 2/6/2021, 60 patients enrolled on this prospective study and 41 completed 6 and 12-month post-treatment assessments after fractionated intensity-modulated proton therapy. Left and right hippocampus volumes were independently measured on T1 sagittal precontrast MRI at baseline, 6-months, and 12-months after radiotherapy using automated software and physician-delineated contours. The relationship between mean hippocampus dose and change in volume was assessed by Pearson’s correlation coefficient. A linear mixed-effects model was applied to evaluate other predictors associated with change in hippocampal volume, assuming random effects of subjects. RESULTS: Mean hippocampus dose was strongly correlated with change in hippocampal volume at 12 months following radiotherapy (r=−0.707, 95% CI [-0.805,-0.572], p&amp;lt;0.001). Changes in hippocampal volumes over time were similar between software and physician contours. In the mixed-effects model, only mean hippocampus dose was significantly associated with hippocampal volume change (p&amp;lt;0.001) at both 6 and 12 months. The final model predicted changes in hippocampal volume of -3.6% and -10.1% for every 10 Gy increase in mean dose at 6 and 12 months, respectively. Hippocampal volume was significantly reduced for mean doses &amp;gt;5 Gy (meanΔ -38.1%±20.3%, p&amp;lt;0.001), while no significant volume change was observed with mean doses ≤5 Gy (meanΔ -1.7%±5.0%). CONCLUSIONS: Change in hippocampal volume was correlated with hippocampus mean dose at 6 and 12 months following radiotherapy. Future analyses will assess volumetric changes in additional brain substructures as a function of radiation dose and correlate with measured neurocognitive and quality-of-life effects.
Extended pelvic lymph node dissection during robotic prostate surgery firmly reduces biochemical recurrence: A propensity score-matched analysis for intermediate- to high-risk prostate cancer
Authors: M. Yashi, M. Yokoyama, G. Nakamura, T. Uematsu, K. Takei, I. Suzuki, K. Sakamoto, D. Nishihara, T. Kijima, T. Kamai
Journal: European Urology (2022)
Efficacy and tolerance of systemic therapies in metastatic melanoma of unknown primary versus known cutaneous: A multicenter retrospective study from the MelBase French Cohort.
Authors: Perrine Rousset, Stéphane Dalle, Laurent Mortier, Olivier Dereure, Sophie Dalac, Caroline Dutriaux, Marie Thérèse Leccia, Delphine Legoupil, Vincent Descamps, Julie De Quatrebarbes, Jean-Jacques Grob, Philippe Saiag, Eve Maubec, Pierre-Emmanuel Stoebner, Florence Granel Brocard, Jean-Philippe Arnault, Clara Allayous, Bastien Oriano, Celeste Lebbe, Henri Montaudie
Journal: Journal of Clinical Oncology (2022)

9556 Background: Melanoma of unknown primary (MUP) account for 3% of all melanomas. Clinical outcome of advanced MUP in the era of novel therapies including immunotherapies (ICI) and targeted therapies (TT) have been only scarcely studied, whereas a possibly different biologic background might introduce changes in its management. Recent retrospective studies suggested that patients with advanced MUP could benefit at least as much from novel therapies as patients with known primary cutaneous melanoma (cMKP). Methods: Based on the nationwide MelBase prospective database (NCT02828202) this retrospective study included patients with advanced melanoma treated with first-line ICI, TT or CT. MUP was defined by upfront occurrence of (sub)cutaneous, nodal and/or visceral metastasis without any known prior or concomitant primary tumor. Patients with primary mucosal or ocular melanoma were excluded. Both progression-free survival (PFS) and overall survival (OS) were analyzed as co-primary variables in MUP vs cMKP, stratified by treatment subset (ICI vs TT vs CT vs whole cohort). Secondary variable was treatment-related toxicity. Multivariate analyses and propensity score analysis were performed. Objective: To investigate the efficacy and safety of systemic treatments (ICI, TT and chemotherapy (CT)) in patients with advanced MUP comparatively to stage-matched cMKP. Results: A total of 1882 patients were analyzed, including 265 (14.1%) MUP. Most patients were treated with first-line ICI. Median follow-up was 16 months. Patients in the MUP cohort more often displayed unfavorable initial prognostic factors (Table). PFS and OS did not significantly differ in MUP compared to MKP patients (p=0.73 and p=0.93 respectively). Stratification of cohorts by treatment type and application of propensity score did not lead to data modification. Treatment-related toxicity rate and severity did not differ between MUP and MKP, regardless of treatment type. Conclusions: Our results suggest that advanced MUP should be managed with similar strategies as advanced MKP. In our cohort, MUP patients benefited from novel therapies as much as MKP patients despite less favorable baseline prognostic factors. Exploratory studies investigating mutational burden and host immunity are needed to identify the underlying mechanisms. [Table: see text]
Clinicopathological features and management of patients with primary CNS lymphoma: Peruvian experience in two cancer centers.
Authors: Melanie Wendy Castro-Mollo, Alonso Diaz, Katia Roque Perez, Jessica Gabriela Meza, Shirley Milenca Quintana Truyenque, Estefanía Peña, Lourdes Lopez, Carlos Barrionuevo, Víctor Iván Mallma Soto, Daniela Dueñas, Cindy Elizabeth Alcarraz, Tatiana Vidaurre, Cesar Augusto Samanez, Jule F Vasquez
Journal: Journal of Clinical Oncology (2022)

e19541 Background: Primary central nervous system lymphoma (PCNSL) is an aggressive and rare extranodal non-Hodgkin lymphoma with a dismal prognosis in most patients. Outcomes in Latin population is unknown. Methods: We present a retrospective cohort of fifty-five and six newly diagnosed Peruvian patients treated at the Instituto Nacional de Enfermedades Neoplasicas from 2000-2020 and at Oncosalud from 2014-2020, respectively. Inclusion criteria were (1) histologic diagnosis of diffuse large B-cell lymphoma by two pathologists; (2) disease localized exclusively in the brain, cranial nerves, meninges, or eyes; and (3) no evidence of human immunodeficiency virus infection. Results: Median age at diagnosis was 52 years old [range 21-76]. Sixty-one percent were men. Eastern Cooperative Oncology Group performance status was ≥2 in 68% of patients. Clinical presentation was characterized by intracranial hypertension symptoms (67%), focal deficit (64%), visual disturbance (18%), and seizures (9%). elevated LDH was present in 26/46 (57%) patients, multiple lesions in 19/56 (34%) patients, and involvement of deep structures 21/62 (34%) patients. Seven patients were treated by surgery only (3, subtotal and 4, total resection), three patients received radiotherapy only, and six patients did not receive any treatment. Forty-two patients received the following chemotherapy protocols: DeAngelis (26%), high-dose methotrexate (HD-MTX) (17%), HD-MTX + high-dose ARAC (HD-ARAC) (36%) and HD- MTX + HD-ARAC + Rituximab (9%), HD-MTX + Rituximab + Temozolomide (TMZ) as induction and consolidation with etoposide (VP16) + HD-ARAC (12%), the latter was used in the private center. Clinical outcomes are described in Table. The median follow-up time was 9m (0.03-248). The median overall survival (OS) was 9.9m, 5y OS was 41.7% (95% CI, 29.2-53.9). The median OS were 6.6m and 67.3m for the public and the private institution, respectively (p=0.02). 5y OS was 34% and 100% in the public and the private center, respectively. Conclusions: Peruvian patients are 15 years younger than those reported in the literature. OS in our cohort is dismal, being poorer in those patients treated at the public center reflecting treatment disparities between the public and private health system. All patients who received HD-MTX+HD-ARAC+TMZ as induction and VP16 +HD-ARAC as consolidation achieved complete response and the median OS was not reached although this can be explained due to a short follow-up time compared to those who received DeAngelis regimen. A longer follow-up is needed to demonstrate if polychemotherapy without radiotherapy is the best treatment in this group of patients.[Table: see text]
Unusual Metastatic Prostate Cancer in Subcarinal Lymph Node and Peritoneal Nodule Found on 18F-PSMA PET/CT With Rising PSA of 0.4 ng/mL
Authors: Mamie Gao, Yang Lu
Journal: Clinical Nuclear Medicine (2022)

Abstract A 79-year-old man with metastatic prostate cancer underwent radical prostatectomy and bilateral lymph node dissection and received multiple lines of systematic treatment for his biopsy-proven peritoneal carcinomatosis. During the disease course, his prostate-specific antigen rose from 0.1 ng/mL to 0.4 ng/mL in 4 months, and testosterone level was &lt;3 ng/dL. Workup 18 F-DCFPyL PET/CT showed unusual prostate-specific membrane antigen–avid, 1.1-cm subcarinal lymph node and a 0.8-cm peritoneal nodule, which were not hypermetabolic on an 18 F-FDG PET/CT 6 days later. This case illustrated the sensitivity for 18 F-DCFPyL PET/CT in detecting metastatic castration-resistant prostate cancer.
Changes in the Long-term Risk of Adverse Outcomes in Patients Treated With Open vs Endovascular Abdominal Aortic Aneurysm Repair
Authors: Art Sedrakyan, Philip P. Goodney, Jialin Mao, Adam W. Beck, Marc L. Schermerhorn
Journal: JAMA Surgery (2022)

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Ongoing monkeypox virus outbreak, Portugal, 29 April to 23 May 2022
Authors: Mariana Perez Duque, Sofia Ribeiro, João Vieira Martins, Pedro Casaca, Pedro Pinto Leite, Margarida Tavares, Kamal Mansinho, Luís Miguel Duque, Cândida Fernandes, Rita Cordeiro, Maria José Borrego, Ana Pelerito, Isabel Lopes de Carvalho, Sofia Núncio, Vera Manageiro, Corrado Minetti, Jorge Machado, Joana M Haussig, Roberto Croci, Gianfranco Spiteri, Ana Sofia Casal, Diana Mendes, Tiago Souto, Sara Pocinho, Teresa Fernandes, Ana Firme, Paula Vasconcelos, Graça Freitas
Journal: Eurosurveillance (2022)

Up to 27 May 2022, Portugal has detected 96 confirmed cases of monkeypox. We describe 27 confirmed cases (median age: 33 years (range: 22–51); all males), with an earliest symptom onset date of 29 April. Almost all cases (n = 25) live in the Lisbon and Tagus Valley health region. Most cases were neither part of identified transmission chains, nor linked to travel or had contact with symptomatic persons or with animals, suggesting the possible previously undetected spread of monkeypox.
Double-drug loading upconversion nanoparticles for monitoring and therapy of a MYC/BCL6-positive double-hit diffuse large B-cell lymphoma
Authors: Yulu Yang, Rui Chen, Yi Gong, Weihu Yang, Ke Li, Wuzhe Fan, Shuangquan Gou, Pengfei Gao, Tingting He, Kaiyong Cai
Journal: Biomaterials (2022)
Coarse Particulate Air Pollution and Daily Mortality: A Global Study in 205 Cities
Authors: Cong Liu, Jing Cai, Renjie Chen, Francesco Sera, Yuming Guo, Shilu Tong, Shanshan Li, Eric Lavigne, Patricia Matus Correa, Nicolas Valdes Ortega, Hans Orru, Marek Maasikmets, Jouni J. K. Jaakkola, Niilo Ryti, Susanne Breitner, Alexandra Schneider, Klea Katsouyanni, Evangelia Samoli, Masahiro Hashizume, Yasushi Honda, Chris Fook Sheng Ng, Magali Hurtado Diaz, César De la Cruz Valencia, Shilpa Rao, Alfonso Diz-Lois Palomares, Susana Pereira da Silva, Joana Madureira, Iulian Horia Holobâc, Simona Fratianni, Noah Scovronick, Rebecca M. Garland, Aurelio Tobias, Carmen Íñiguez, Bertil Forsberg, Christofer Åström, Ana Maria Vicedo-Cabrera, Martina S. Ragettli, Yue-Liang Leon Guo, Shih-Chun Pan, Ai Milojevic, Michelle L. Bell, Antonella Zanobetti, Joel Schwartz, Antonio Gasparrini, Haidong Kan
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: The associations between ambient coarse particulate matter (PM2.5–10) and daily mortality are not fully understood on a global scale. Objectives: To evaluate the short-term associations between PM2.5–10 and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide. Methods: We collected daily mortality (total, cardiovascular, and respiratory) and air pollution data from 205 cities in 20 countries/regions. Concentrations of PM2.5–10 were computed as the difference between inhalable and fine PM. A two-stage time-series analytic approach was applied, with overdispersed generalized linear models and multilevel meta-analysis. We fitted two-pollutant models to test the independent effect of PM2.5–10 from copollutants (fine PM, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide). Exposure–response relationship curves were pooled, and regional analyses were conducted. Measurements and Main Results: A 10 μg/m3 increase in PM2.5–10 concentration on lag 0–1 day was associated with increments of 0.51% (95% confidence interval [CI], 0.18%–0.84%), 0.43% (95% CI, 0.15%–0.71%), and 0.41% (95% CI, 0.06%–0.77%) in total, cardiovascular, and respiratory mortality, respectively. The associations varied by country and region. These associations were robust to adjustment by all copollutants in two-pollutant models, especially for PM2.5. The exposure–response curves for total, cardiovascular, and respiratory mortality were positive, with steeper slopes at lower exposure ranges and without discernible thresholds. Conclusions: This study provides novel global evidence on the robust and independent associations between short-term exposure to ambient PM2.5–10 and total, cardiovascular, and respiratory mortality, suggesting the need to establish a unique guideline or regulatory limit for daily concentrations of PM2.5–10.
Inference of sample-specific genetic interactions to increase accuracy of indication prioritization in oncology clinical trials and facilitate exploration of combined therapy opportunities.
Authors: Sarah Jenna, Audrey Lemaçon, Mehrnoush Dehghani, Sébastien Renaut, Abdoulaye Baniré Diallo
Journal: Journal of Clinical Oncology (2022)

3123 Background: Precision oncology is growing rapidly in parallel with advances in high throughput sequencing. Development of new anti-cancer therapies is, however, still associated with low efficacy issues, leading to phase II and III clinical trial failures. Improved methodologies are required to identify clinical and molecular patient profiles associated with good drug response to inform decisions on indication prioritization. Methods: We used a sample-specific Genetic Interaction Graph Inference (ssGI 2 ) algorithm, integrating bulk tumor transcriptomic data as well as data collected from 120 public databases and scientific literature in oncology, to infer genetic interactions (GI). More than 10,000 genes from 17,000 samples, covering 195 oncology ICD10 codes, were used to infer GIs for each individual sample. GIs involving a given drug target are selected from a compendium of 17,000 networks of 2M GIs each, and ranked based on their prevalence in the patient cohort and data-support. The mean Z-scored expression of genes from the top ranked GIs were subsequently used to predict drug response for each patient and to calculate the response rate for each indication. Detailed information on each drug target’s genetic interactors was used to characterize the drug’s mechanisms of action and explore opportunities for combined therapies. We investigated our method's ability to predict good responders using four FDA approved immune and targeted therapies (pembrolizumab, nivolumab, ipilimumab and sorafenib) across seven clinical studies. Importantly this methodology is suitable for drugs with no clinical studies available. Results: Our results show that the prediction of good responders can be achieved with Precision-Recall AUC on average 13% higher than predictions based on drug target expression level solely, in five out of seven studies. Also, for each drug target, between 30 to 140 genetic interactors with good performance (Precision=0.92; Recall=0.61) were identified, suggesting potential synergistic effects of drugs, some of which have already been confirmed by clinical studies on combined therapies. Conclusions: Our ssGI 2 -derived signatures are powerful predictors of good response to a drug even without available clinical data. Applying this methodology at a pre-clinical stage will significantly de-risk clinical trials, particularly for novel therapies, and could also support investigation of new combined therapies.
An alpha-fetoprotein-maytansine conjugate for the treatment of AFP receptor expressing tumors.
Authors: Igor A. Sherman, Rebecca J Boohaker, Karr Stinson, Patricia Griffin, Wendy Hill
Journal: Journal of Clinical Oncology (2022)

e15056 Background: The alpha fetoprotein (AFP) receptor is an oncofetal antigen and a novel target for cancer therapeutics. It is highly expressed on the surfaces of many cancers and myeloid derived suppressor cells (MDSCs) but absent on normal tissues. By conjugating a novel maytansinoid toxin to a recombinant form of human AFP (ACT-101), we can selectively deliver the toxin to cancer and MDSC cells while sparing normal cells, thereby enabling a combination of targeted and immune activating approaches against the tumor. Methods: Four ACT-101-maytansinoid conjugates with different protein-toxin ratios and different linker chemistries were initially investigated in a mouse COLO-205 xenograft model, resulting in the selection of ACT-903 as the lead candidate for further development. A second study performed in the same tumor model compared the effects of single intravenous doses of ACT-903 (10-50 mg/kg) to control groups receiving either vehicle or the unconjugated protein, ACT-101 (25 mg/kg). Tumor growth, survival and clinical observations were assessed for 60 days post tumor implantation. Both serum ACT-101 and maytansinoid levels were measured following the single dose. Results: In the first study, a statistically significant reduction in tumor volume was seen for all four conjugates compared to vehicle control (p &lt; 0.05). For ACT-903, tumors continued shrinking even after treatment completion, becoming undetectable in 9 of 10 animals. All 10 mice in this group survived through Day 60 with no obvious signs of toxicity. In contrast, there were no survivors in the control group. In the single dose study of ACT-903, a significant reduction of tumor burden compared to vehicle was achieved by Day 14 (p &lt; 0.05) in both the 40 and 50 mg/kg dose groups. Mice in these 2 groups received a second dose 15 days after the first dose, based on observed tumor re-growth. Survival was significantly prolonged in the 50 mg/kg (p = 0.0037) and 40 mg/kg group (p &lt; 0.0001) with 7 of 10 in the 50 mg/kg group and 9 of 10 animals in the 40 mg/kg group surviving to Day 60. Similar doses of ACT-101 and ACT-903 produced comparable ACT-101 serum levels, suggesting that the pharmacokinetic profile of the conjugate is driven primarily by the protein component. Free maytansinoid levels at 4 hours were less than 0.01% of the injected dose of the conjugate, indicating that the conjugate is stable in circulation. Conclusions: The efficacy and tolerability of ACT-903 in an animal tumor model supports advancing this conjugate toward clinical use with a regimen of either once a week or once every other week administration.